Open Access Research

Respiratory infection of mice with mammalian reoviruses causes systemic infection with age and strain dependent pneumonia and encephalitis

Lianne Gauvin1, Steffany Bennett1, Hong Liu1, Mansoureh Hakimi3,4,5, Michael Schlossmacher3,4, Jay Majithia1 and Earl G Brown1,2*

Author Affiliations

1 Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Rd, Ottawa, Ontario K1H 8M5, Canada

2 Emerging Pathogens Research Centre, University of Ottawa, 451 Smyth Rd, Ottawa, Ontario K1H 8M5, Canada

3 Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, 451 Smyth Rd, Ottawa, Ontario K1H 8M5, Canada

4 Program in Neuroscience, Ottawa Hospital Research Institute University of Ottawa, 451 Smyth Road, RGN #1412, Ottawa, ON K1H 8M5, Canada

5 Division of Neurology, The Ottawa Hospital, University of Ottawa, 451 Smyth Road, RGN #1412, Ottawa, ON K1H 8M5, Canada

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Virology Journal 2013, 10:67 doi:10.1186/1743-422X-10-67

Published: 1 March 2013

Abstract

Background

Because mammalian reoviruses are isolated from the respiratory tract we modeled the natural history of respiratory infection of adult and suckling mice with T1 Lang (T1L) and T3 Dearing (T3D) reoviruses.

Methods

Adult and suckling Balb/c mice were infected by the intranasal route and were assessed for dose response of disease as well as viral replication in the lung and other organs. Viral antigen was assessed by immunofluorescence and HRP staining of tissue sections and histopathology was assessed on formalin fixed, H + E stained tissue sections.

Results

Intranasal infection of adult mice resulted in fatal respiratory distress for high doses (107 pfu) of T1L but not T3D. In contrast both T1L and T3D killed suckling mice at moderate viral dosages (105 pfu) but differed in clinical symptoms where T1L induced respiratory failure and T3D caused encephalitis. Infections caused transient viremia that resulted in spread to peripheral tissues where disease correlated with virus replication, and pathology. Immunofluorescent staining of viral antigens in the lung showed reovirus infection was primarily associated with alveoli with lesser involvement of bronchiolar epithelium. Immunofluorescent and HRP staining of viral antigens in brain showed infection of neurons by T3D and glial cells by T1L.

Conclusions

These mouse models of reovirus respiratory infection demonstrated age and strain dependent disease that are expected to be relevant to understanding and modulating natural and therapeutic reovirus infections in humans.

Keywords:
Mammalian reovirus; Pathogenesis; Pneumonia; Systemic infection; Intranasal infection; Serotype 3 Dearing; Serotype 1 Lang; Encephalitis; Immunofluorescence; Liver; Lung; Suckling mouse; Viremia